The competitive landscape for biopharmaceuticals always seems to be heating up. Internally developed assets are rarely enough to sustain growth, and this fact eventually drives companies to look beyond their own four R&D walls to identify targeted development opportunities. Over time, those companies that demonstrate competitive advantage in how they assess, decide upon, and take advantage of in-licensing deals will be the ones delivering outsized value to patients.
The clinical supply chain has a crucial role to play concerning both due diligence supporting potential in-licensing deals, and the subsequent on boarding of new assets. Unfortunately, their role is often overlooked. This can be a costly mistake, since supply chain input can often make the difference between dramatic success and catastrophic failure where cultivating new therapies is concerned. By mapping out the various considerations to entertain, and questions to answer for Business Development (BD) and executive leadership, this article seeks to define how clinical supply leadership can add value to due diligence situations. After this, broad considerations are provided to help these leaders absorb new assets into their pipeline of work.
Understanding the Driving Elements of Supply and Demand
It’s obvious but worth stating: before signing up for something, determine what you might be getting yourself into. Numerous business functions will be involved in this analysis, primarily BD, but also Legal (IP particularly), Finance, Commercial, and R&D. From the Supply Chain Leadership (SCL) perspective, understanding the contours of a potential new asset deal means contemplating the outlines of what a clinical development plan would look like. When would the investigational medicinal product (IMP) be required, and will any inventory be inherited if a deal goes through? If so, do you know that this inventory would be fit for use?
For example, some companies inherit inventory that has ink-jetting printed on material (say, on vials or on the bottom of bottles) that precludes its use in blinded situations unless costly GMP operations are undertaken. Asking the right questions during due diligence can avoid these types of surprises. As well, are there expectations for expensive comparator or combination therapy requirements? It’s not unheard of for companies to determine, after a deal is struck, that additional funding (sometimes hundreds of millions of dollars) will be required to run a head-to-head phase III against another company’s medicine. Knowing this going into the deal would have changed the decision calculus significantly. Understanding these supply and demand driving elements are a critical part of preliminary budgeting – a key component of cost-benefit analysis.
However, accurate costing is only one part of the analytical value that SCL provides in these situations. From a risk and complexity standpoint, you will wish to understand what partnerships you would be signing up to maintain (i.e. those in which you’ll initially have no choice in the matter), and what in-flight activities and systems would need to be taken over. The quality and operational risks that come with being forced into particular vendor partnerships, as well as risks involving expedited handoffs and unfamiliar systems, are better highlighted early on rather than after the ink is dry.
Finally, what would the plan be? When would various types of manufacturing and manufacturing decisions be required, and what information would feed into those decisions? Mapping this out can drive crucial preliminary analysis on questions of scale, manufacturing capacity and global procurement. If it is going to be impossible to maintain supply continuity, that’s a critical due diligence input best provided by supply chain professionals. They are the only ones capable of ensuring proper translation of program demand into production planning.
There are many other due diligence questions that can, and should, be considered from a supply chain perspective. A few include the following:
- Are there any special manufacturing considerations such as safety of material handling, management of controlled substances, etc.? Are there any special types of ancillaries or lab supplies that would be required for dosing patients? Can these be procured or is there a shortage in the market?
- What testing sites and partners have been used previously, or would we intend to use? Are there regulatory filings which would be required to support them? How much stability data will exist on the medicinal product and will inherited inventory have usable shelf life?
- What packaging configuration has been used previously, and what will be used going forward? Is the dosage form and primary packaging fit for the use we would intend? Will we be able to obtain full genealogy information for past clinical use of supply?
Once the Ink is Dry
Once the ink is dry, the real work begins. As assumptions are turned into project management, effective brainstorming of all necessary work becomes key. Although every program is different, it’s crucial to have collaborative discussions with team members who have been through on boarding a new asset before. What contracts and agreements need to be put in place, and with whom, in order to move forward various types of work? How helpful can you expect the transitioning party to be, where elements such as knowledge and document transfer are concerned? As the overall transition process begins, both internal and external relationships need to be managed with care. Taking time to agree on responsibilities, norms and expectations is usually time well spent.
Beyond relationships, operational strategy will need to be firmed up. What supply chain decisions are you driving toward, and what information will be required to support them? Have those decisions you believe were previously made (i.e. things assumed at point of signing) been properly socialized, vetted, and documented such they won’t be revisited later? Can a risk matrix be built, and a plan fleshed out to deal with those risks as fully as possible?
The Devil is in the Details
If this all seems like quite a bit of question asking, that’s because it is. The more time spent understanding your questions – and the various considerations that will need to be taken into account when answering them – the more efficient the actual work of operations will be. That being said, eventually several things will need to occur to support further development of the asset:
- Ownership of any existing (purchased as part of the agreement) inventory will need to be transferred. This may involve additional agreements requiring signoff from your legal team
- Supply chain forecasts will need to be fleshed out, based on revised clinical development needs as well as any non-clinical needs for material. Refined budgeting and resource estimation should take place during this planning cycle
- Manufacturing will need to be scheduled. Suppliers will need to be brought into your system, along with any necessary setups to support production. Audits, specification development, and lab contracts will often be required
- Lifecycle management, network and scale decisions will need to be made. Tech transfer timelines will need to be considered. And shelf-life planning is always essential
Do not underestimate any of the work involved in the activities above. The cross-functional work of drug development is a constant war of staying off the critical pathway to patients, and numerous activities always take longer than you think they should. Special allotments of expected time should be given to anything requiring legal review, or anything requiring endorsement from a team that meets only at scheduled intervals (executive teams, for example).
Furthermore, just because you are going to be ready to produce medicine at a certain point in time, doesn’t mean your partner will have manufacturing capacity at that point. Finally, when you are producing something even slightly new, in terms of process, don’t underestimate the amount of stability data that will be required in order to make arguments for shelf life comparable to previous supply (it’s often best to assume six months’ worth of data).
The supply chain has a key role to play in both due diligence assessment prior to in-licensing, and on boarding of newly acquired therapeutic assets. As they say, the devil is in the details. While no team is all-knowing, understanding the right questions to ask, and considerations at play, will help pave the way to successfully helping patients down the road.